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19 pages, 7043 KiB  
Article
Flow Cytometry Analyses of Meningioma Immune Cell Composition Using a Short, Optimized Digestion Protocol
by Gillian Dao Nyesiga, Jeppe Lohfert Haslund-Vinding, Josephine Budde, Josefine Føns Lange, Nadja Blum, Kotryna Dukstaite, Lars Ohlsson, Tiit Mathiesen, Anders Woetmann and Frederik Vilhardt
Cancers 2024, 16(23), 3942; https://doi.org/10.3390/cancers16233942 (registering DOI) - 25 Nov 2024
Viewed by 145
Abstract
Background: Current challenges in meningioma treatment, including post-surgical complications and cognitive impairments, highlight the need for new treatment alternatives. Immunological interventions have shown promise. However, there is a knowledge gap in characterizing infiltrating immune cells in meningioma and their interplay. Further studies on [...] Read more.
Background: Current challenges in meningioma treatment, including post-surgical complications and cognitive impairments, highlight the need for new treatment alternatives. Immunological interventions have shown promise. However, there is a knowledge gap in characterizing infiltrating immune cells in meningioma and their interplay. Further studies on immune cells in single-cell suspensions from digested meningioma tissues could identify targetable mechanisms for non-surgical treatment options with fewer side effects. This study aimed to optimize a protocol for faster digestion of meningioma tissues into viable single-cell suspensions and to identify infiltrating immune cell populations. Methods: We modified a commercial kit intended for whole skin dissociation to digest resected meningioma tissues into viable single-cell suspensions. Tumor-infiltrating immune cell populations were characterized using flow cytometry. Results: Flow cytometry analyses revealed that the digested tissue was composed of viable immune cells, including predominantly CD14+ macrophages and CD3+ T cells, with minor populations of CD56+ NK cells and CD19+ B cells. In both of the two patient samples tested, half of the tumor-associated macrophages were TIM-3+, with a small proportion co-expressing CD83. Women were more likely to have a lower proportion of immune cells, B cells, and NK cells. Female patients with a high proportion of immune cells had a higher proportion of macrophages. Conclusion: We successfully optimized a protocol for generating single-cell suspensions with viable immune cells from meningioma tissues, revealing infiltrating antigen-presenting cells with an immunosuppressive phenotype, and lymphocytes. This short protocol allows advanced analyses of tumor-infiltrating cells using techniques such as single-cell RNA sequencing and flow cytometry, which require live, dissociated cells. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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Figure 1

Figure 1
<p>An overview of the optimized protocol for digestion of meningioma for viable single-cell suspensions comprising immune cells. The illustration was created using BioRender.</p>
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<p>Assessment of cell suspension after digesting meningioma using flow cytometry. (<b>A</b>) Gating strategy for the samples from flow cytometry analyses. (<b>B</b>) Viability of single cells without debris clouds and (<b>C</b>) proportion of CD45<sup>+</sup> immune cells after meningioma tumors were incubated in digestion reagents for 10, 20, 30, and 40 min. See <a href="#app1-cancers-16-03942" class="html-app">Supplementary Figure S1</a> for more data. (<b>D</b>) The viability of single cell without debris clouds, and the proportion of CD45<sup>+</sup> immune cells of digested meningioma samples. (<b>E</b>,<b>F</b>) Samples digested the same day (fresh) compared to samples digested the next day (O/N) assessed (<b>E</b>) via the viability of single cells and (<b>F</b>) via the proportion of CD45<sup>+</sup> immune cells. Data is presented as individual values ((<b>B</b>,<b>C</b>) with <span class="html-italic">n</span> = 1 from 1 experiment) or as mean with SEM ((<b>D</b>) with <span class="html-italic">n</span> = 20 from 15 experiments, and (<b>E</b>,<b>F</b>) with <span class="html-italic">n</span> = 7 from 7 experiments) for Fresh and <span class="html-italic">n</span> = 13 with 9 experiments for O/N. An unpaired <span class="html-italic">t</span>-test was used for statistical comparisons. Statistical significances are presented as ns = non-significant.</p>
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<p>An overview of the myeloid compartment of the digested meningioma tissue using flow cytometry. Debris, doublets, and dead cells were excluded before the CD45<sup>+</sup> gate (as shown in <a href="#cancers-16-03942-f002" class="html-fig">Figure 2</a>A). (<b>A</b>) The gating strategy for <a href="#cancers-16-03942-f003" class="html-fig">Figure 3</a>D. (<b>B</b>) The gating strategy for <a href="#cancers-16-03942-f003" class="html-fig">Figure 3</a>E. (<b>C</b>) The gating strategy for <a href="#cancers-16-03942-f003" class="html-fig">Figure 3</a>F. (<b>D</b>) The proportion of CD11c<sup>+</sup> cells, CD14<sup>+</sup> cells, and CD64<sup>+</sup> cells of viable CD45<sup>+</sup> immune cells. (<b>E</b>) Proportions of CD11c<sup>+</sup>CD14<sup>+</sup>, CD14<sup>+</sup>HLA-DR<sup>+</sup>, and CD11c<sup>+</sup>HLA-DR<sup>+</sup> cells. (<b>F</b>) HLA-DR<sup>+</sup> and CD64<sup>+</sup> cells of CD11c<sup>+</sup>CD14<sup>+</sup> cells. Data is presented as mean with SEM ((<b>D</b>) with <span class="html-italic">n</span> = 17 from 10 experiments for CD11c, <span class="html-italic">n</span> = 19 from 12 experiments for CD14, <span class="html-italic">n</span> = 9 from 6 experiments for HLA-DR, and <span class="html-italic">n</span> = 4 from 2 experiments for CD64; (<b>E</b>) with <span class="html-italic">n</span> = 15 from 9 experiments for CD11c<sup>+</sup>CD14<sup>+</sup>, <span class="html-italic">n</span> = 9 from 6 experiments for CD14<sup>+</sup>HLA-DR<sup>+</sup>, and <span class="html-italic">n</span> = 9 from 6 experiments; and (<b>F</b>) with <span class="html-italic">n</span> = 9 from 6 experiments for HLA-DR and <span class="html-italic">n</span> = 4 from 2 experiments. Either a <span class="html-italic">t</span>-test or one-way ANOVA with post-hoc testing was used for statistical comparisons. Statistical significances are presented as ns = non-significant.</p>
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<p>The expression of TIM-3 and CD83 in CD45<sup>+</sup> immune cells was assessed using flow cytometry. (<b>A</b>) CD14/TIM-3 of viable CD45<sup>+</sup> cells. (<b>B</b>) CD14/CD83 of viable CD45<sup>+</sup> immune cells. (<b>C</b>) CD14 of viable CD45<sup>+</sup> cells. (<b>D</b>) CD4 of viable CD45<sup>+</sup> cells. (<b>E</b>) CD14/CD4 of viable CD45<sup>+</sup> cells. (<b>F</b>) CD83/TIM-3 of CD14<sup>+</sup>CD4<sup>+</sup> cells. Representative data for 2 patients with WHO grade 1 meningioma from 2 experiments.</p>
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<p>Overview of the lymphoid compartment. (<b>A</b>) The gating strategy for the flow cytometric analyses. (<b>B</b>) T cell proportion of CD45<sup>+</sup> immune cells. (<b>C</b>) The proportion of CD4<sup>+</sup> helper T cells and CD8<sup>+</sup> cytotoxic T cells. (<b>D</b>) The proportion of CD19<sup>+</sup> B cells. (<b>E</b>) The proportion of CD56<sup>+</sup> NK cells. Data is presented as mean with SEM ((<b>B</b>) with <span class="html-italic">n</span> = 5 from 4 experiments, (<b>C</b>) with <span class="html-italic">n</span> = 3 from 3 experiments, (<b>D</b>) with <span class="html-italic">n</span> = 22 from 14 experiments, and (<b>E</b>) with <span class="html-italic">n</span> = 12 from 7 experiments). A <span class="html-italic">t</span>-test was used for statistical comparison. Statistical significances are presented as ** = <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Assessment of CD45RA and CD45RO expression on immune cells within meningioma. (<b>A</b>) The gating strategy for the flow cytometry analyses. The proportion of CD45RA and CD45RO of the following populations: (<b>B</b>) CD45<sup>+</sup> cells, (<b>C</b>) CD4<sup>+</sup> cells, (<b>D</b>) CD8<sup>+</sup> cells, and (<b>E</b>) CD4<sup>−</sup>CD8<sup>−</sup> cells. Data is presented as mean with SEM ((<b>B</b>–<b>E</b>) with <span class="html-italic">n</span> = 15 from 13 experiments), and a <span class="html-italic">t</span>-test was used for statistical comparisons. Statistical significances are presented as * = <span class="html-italic">p</span> &lt; 0.05 and **** = <span class="html-italic">p</span> &lt; 0.0001.</p>
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9 pages, 1110 KiB  
Article
Ex Vivo Fluorescence Confocal Microscopy Meets Innovation and Revolutionary Technology, for “Real-Time” Histological Evaluation, in Pediatric Surgical Oncology
by Donatella Di Fabrizio, Edoardo Bindi, Michele Ilari, Alessandra Filosa, Gaia Goteri and Giovanni Cobellis
Children 2024, 11(12), 1417; https://doi.org/10.3390/children11121417 - 23 Nov 2024
Viewed by 348
Abstract
Background and Aim: Ex vivo fluorescence confocal microscopy (FCM) systems are innovative optical imaging tools that create virtual high-resolution histological images without any standard tissue processing, either freezing or fixing in formalin and embedding in paraffin. These systems have opened an era that [...] Read more.
Background and Aim: Ex vivo fluorescence confocal microscopy (FCM) systems are innovative optical imaging tools that create virtual high-resolution histological images without any standard tissue processing, either freezing or fixing in formalin and embedding in paraffin. These systems have opened an era that would revolutionize pathological examination by providing rapid, real-time assessments across various pathology subspecialties, potentially replacing conventional methods that are tissue- and time-consuming. This study aimed to present the first utilization of FCM in pediatric surgical oncology, focusing on assessing the benefits, particularly in facilitating rapid and accurate diagnosis. Methods: This preliminary study comprised five consecutive patients undergoing surgical biopsy for disease characterization and surgical strategy selection. After biopsy, tissue samples were prepared and analyzed using FCM without sectioning. A pathologist who evaluated macroscopic and microscopic images, once obtained remotely, could promptly indicate any interventions that require timeliness. Samples were then evaluated with conventional methods. Results: All five lesions were deemed suitable for evaluation. Preliminary diagnoses utilizing FCM included atypical Spitz nevus (1), Wilm’s tumor (1), lymph node reactive hyperplasia (1), malignant germ cell tumor of the testis (1), and Hodgkin’s lymphoma (1). Final histopathological analyses revealed atypical Spitz nevus (1), Wilm’s tumor (1), hyperplastic lymphadenopathy with a prevalent marginal pattern (1), mixed nonseminomatous malignant germinal neoplasm consisting of embryonal carcinoma (90%) and yolk sac tumor (10%), and Hodgkin’s lymphoma nodular sclerosis variant (1). In the case of diagnosis of atypical Spitz nevus, the widening of the resection margins was performed in the same surgery. In the case of testicular neoplasm, radical orchiectomy was performed. A high level of agreement between FCM evaluation and definitive histological examination was observed for all parameters evaluated. Conclusions: FCM represents a significant advancement in pathological imaging technology, offering potential benefits in enhancing traditional tissue processing methods. This preliminary report marks the first application of FCM in pediatric surgical oncology. Our findings underscore the promising role of FCM as an adjunctive tool in pediatric oncology, facilitating prompt diagnosis and treatment initiation. Full article
(This article belongs to the Special Issue Diagnosis and Surgical Care of Pediatric Cancers)
16 pages, 322 KiB  
Review
The ‘Liaisons dangereuses’ Between Lung Cancer and Interstitial Lung Diseases: A Focus on Acute Exacerbation
by Umberto Zanini, Paola Faverio, Valentina Bonfanti, Maria Falzone, Diego Cortinovis, Stefano Arcangeli, Francesco Petrella, Giovanni Ferrara, Marco Mura and Fabrizio Luppi
J. Clin. Med. 2024, 13(23), 7085; https://doi.org/10.3390/jcm13237085 (registering DOI) - 23 Nov 2024
Viewed by 200
Abstract
Patients with interstitial lung disease (ILD) are about five times more likely to develop lung cancer than those without ILD. The presence of ILD in lung cancer patients complicates diagnosis and management, resulting in lower survival rates. Diagnostic and treatment procedures needed for [...] Read more.
Patients with interstitial lung disease (ILD) are about five times more likely to develop lung cancer than those without ILD. The presence of ILD in lung cancer patients complicates diagnosis and management, resulting in lower survival rates. Diagnostic and treatment procedures needed for cancer can increase the risk of acute exacerbation (AE), one of the most severe complications for these patients. Bronchoscopic techniques are generally considered safe, but they can trigger AE-ILD, particularly after cryoprobe biopsies. Surgical procedures for lung cancer, including lung biopsies and resections, carry an elevated risk of AE-ILD. Postoperative complications and mortality rates highlight the importance of meticulous surgical planning and postoperative care. Furthermore, cancer treatments, such as chemotherapy, are all burdened by a risk of AE-ILD occurrence. Radiotherapy is important for managing both early-stage and advanced lung cancer, but it also poses risks. Stereotactic body radiation and particle beam therapies have varying degrees of safety, with the latter potentially offering a lower risk of AE. Percutaneous ablation techniques can help patients who are not eligible for surgery. However, these procedures may complicate ILD, and their associated risks still need to be fully understood, necessitating further research for improved safety. Overall, while advancements in lung cancer treatment have improved outcomes for many patients, the complexity of managing patients with concomitant ILD needs careful consideration and multidisciplinary assessment. This review provides a detailed evaluation of these risks, emphasizing the need for personalized treatment approaches and monitoring to improve patient outcomes in this challenging population. Full article
(This article belongs to the Section Pulmonology)
8 pages, 5591 KiB  
Case Report
A Case of B-Cell Lymphoblastic Lymphoma Presenting with an Isolated Epidural Mass Treated Successfully with Radiotherapy Followed by United Kingdom Acute Lymphoblastic Leukemia (UKALL) Chemotherapy Protocol
by Musa Fares Alzahrani
Hematol. Rep. 2024, 16(4), 724-731; https://doi.org/10.3390/hematolrep16040069 (registering DOI) - 23 Nov 2024
Viewed by 251
Abstract
Background: B-cell lymphoblastic lymphoma (B-LBL) is an aggressive type of non-Hodgkin lymphoma that usually involves lymph nodes, skin and soft tissue. Bone marrow and peripheral blood are normally spared from involvement in the disease. B-LBL typically forms solid masses that have similar pathologic [...] Read more.
Background: B-cell lymphoblastic lymphoma (B-LBL) is an aggressive type of non-Hodgkin lymphoma that usually involves lymph nodes, skin and soft tissue. Bone marrow and peripheral blood are normally spared from involvement in the disease. B-LBL typically forms solid masses that have similar pathologic and immunophenotypic features to their liquid counterpart, B-cell acute lymphoblastic leukemia (B-ALL). The presentation of B-LBL with a solitary epidural mass at the cervical spine is very rare and the optimal treatment of such cases is unknown. Most of the literature on the management of B-LBL comes from small case series, pediatric patients, or as part of retrospective data that combine B-LBL with B-ALL cases. Case presentation: The case presented herein is a unique presentation that was treated using three modalities, namely surgical resection, radiotherapy and consolidation with systemic chemotherapy, adopted from the United Kingdom acute lymphoblastic leukemia (UKALL14) protocol. Conclusions: The patient attained complete remission following the planned treatment and is still in remission for more than four and half years from the time of his initial diagnosis. Full article
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Figure 1
<p>MRI of the cervical spine showed that there is an intraspinal epidural mass (red arrows) measuring 1.2 × 1.8 × 3.2 mm (AP, TV and CC diameters) in the ventrolateral aspect at the level of C3–C4 extending to the left neural foramen, impinging the adjacent nerve root and compressing the spinal cord with cervical myelopathy. The mass demonstrates avid homogeneous enhancement in postcontrast study and DWI restriction. Abbreviation: Magnetic resonance imaging (MRI), anteroposterior (AP), transverse (TV), and craniocaudal (CC) planes.</p>
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<p>(<b>A</b>) High power microscopic view of lymphoblastic lymphoma. Note the presence of numerous monotonous lymphoid cells showing irregular nuclei, fine nuclear chromatin and conspicuous nucleoli in some cells. [Hematoxylin/Eosin (H/E) stain ×600 magnification (Mag)]. (<b>B</b>) TdT Immunohistochemical stain. Note the strong positive nuclear staining. Mag ×600. (<b>C</b>) Strong positive membranous staining of the lymphoma cells with CD79A confirming the B cell lineage of these cells. Mag ×600. (<b>D</b>) Strong positive cytoplasmatic and membranous staining with CD99 stain. This stain, although not specific, is commonly positive in cases of lymphoblastic lymphoma. Mag ×600.</p>
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<p>(<b>A</b>) High power microscopic view of lymphoblastic lymphoma. Note the presence of numerous monotonous lymphoid cells showing irregular nuclei, fine nuclear chromatin and conspicuous nucleoli in some cells. [Hematoxylin/Eosin (H/E) stain ×600 magnification (Mag)]. (<b>B</b>) TdT Immunohistochemical stain. Note the strong positive nuclear staining. Mag ×600. (<b>C</b>) Strong positive membranous staining of the lymphoma cells with CD79A confirming the B cell lineage of these cells. Mag ×600. (<b>D</b>) Strong positive cytoplasmatic and membranous staining with CD99 stain. This stain, although not specific, is commonly positive in cases of lymphoblastic lymphoma. Mag ×600.</p>
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<p>Follow up MRI Showed that there has been interval laminectomy performed at C3–C5 levels, resolution of the large intraspinal anterior epidural mass on the ventrolateral aspect of the canal at the level of C3–C4, improvement of the signal alteration within spinal cord due to cord myelopathy, no significant diffusion restriction, stable faint mild enhancement of C4 vertebra and new alteration on T1 and T2-weighted images at C2 to C6 vertebrae related to radiotherapy.</p>
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17 pages, 1045 KiB  
Review
The Role of Radiation, Immunotherapy, and Chemotherapy in the Management of Locally Advanced or Metastatic Cutaneous Malignancies
by Irini Yacoub, Kareem Rayn, J. Isabelle Choi, Richard Bakst, Arpit Chhabra, Joshua Y. Qian, Peter Johnstone and Charles B. Simone
Cancers 2024, 16(23), 3920; https://doi.org/10.3390/cancers16233920 - 22 Nov 2024
Viewed by 385
Abstract
Introduction: Skin cancer impacts a significant proportion of the population. While surgical management is often the mainstay of treatment, advanced or metastatic cutaneous malignancies require additional local and/or systemic therapies. Methods: A review of the literature was performed studying the use of radiation [...] Read more.
Introduction: Skin cancer impacts a significant proportion of the population. While surgical management is often the mainstay of treatment, advanced or metastatic cutaneous malignancies require additional local and/or systemic therapies. Methods: A review of the literature was performed studying the use of radiation therapy, chemotherapy, and immunotherapy for locally advanced or metastatic cutaneous malignancies. Results: A summary of the present literature on the management of locally advanced or metastatic cutaneous malignancies is presented across cutaneous head and neck basal cell carcinoma, squamous cell carcinoma, melanoma, and Merkel cell carcinoma. The addition of multidisciplinary therapies to resection is often associated with improved outcomes. Conclusion: The management of cutaneous head and neck malignancies requires an approach integrating multiple specialties, to optimize outcomes and minimize toxicities. Full article
(This article belongs to the Special Issue New Concepts and Recent Advances in the Management of Skin Cancer)
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<p>Hedgehog signaling pathway demonstrating pharmacologic inhibitors of the signaling cascade and its molecular targets [<a href="#B25-cancers-16-03920" class="html-bibr">25</a>].</p>
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<p>Mechanism of action of PD-1 and PD-L1 inhibitors. Tumor cells express PD-L1, which interacts with PD-1 on T cells, inhibiting the T cells’ ability to attack the tumor cells (<b>left</b>). PD-1 and PD-L1 inhibitors block this interaction, allowing T cells to effectively eliminate tumor cells (<b>right</b>). PD-1 = programmed cell death protein 1; PD-L1 = programmed cell death ligand 1. For the National Cancer Institute © 2015 Terese Winslow LLC, U.S. Govt. has certain rights.</p>
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15 pages, 452 KiB  
Systematic Review
Primary Extradural Meningioma: A Systematic Review of Diagnostic Features, Clinical Management, and Surgical Outcomes
by Kishore Balasubramanian, Jeffrey A. Zuccato, Abdurrahman F. Kharbat, Christopher Janssen, Nancy M. Gonzalez and Ian F. Dunn
Cancers 2024, 16(23), 3915; https://doi.org/10.3390/cancers16233915 - 22 Nov 2024
Viewed by 315
Abstract
Objective: This systematic review consolidates the literature on primary extradural meningiomas (PEMs), a rare subset of meningiomas. We describe the clinical features, management strategies used, and treatment outcomes for published cases. Methods: A systematic review was conducted using PRISMA guidelines across multiple databases [...] Read more.
Objective: This systematic review consolidates the literature on primary extradural meningiomas (PEMs), a rare subset of meningiomas. We describe the clinical features, management strategies used, and treatment outcomes for published cases. Methods: A systematic review was conducted using PRISMA guidelines across multiple databases to 29 July 2024. Inclusion criteria were adult patients with primarily extradural meningioma and where individual patient clinical data were provided. Results: Of 216 studies that met the initial search criteria, 41 satisfied the final inclusion criteria. These 41 studies included 82 patients with 84 total PEMs. The cohort was balanced between sexes with a median age of 46 (range 18–82). Frequent symptoms at initial presentation included pain/headache (46%), weakness (44%), paresthesias (24%), and a palpable superficial mass (23%). The median duration of symptoms to diagnosis was 11 months (range 0.75–120). Surgical resection was the primary treatment approach, achieving a gross total resection in 67% of cases. The majority of lesions were classified as WHO grade 1 (87%). A recurrence was identified during the published follow-up in 11% of cases and a higher WHO grade was expectedly associated with a greater risk of recurrence. The described practice was to use adjuvant radiotherapy in recurrent and high-grade cases. Most cranial lesions were located in the frontal bone, while most spinal lesions affected the cervical spine. Post-treatment symptom improvement or resolution was described in almost all patients at the last follow-up. Conclusions: In comparison to intradural meningiomas, PEMs largely follow a more indolent course with a longer duration of symptoms prior to diagnosis, more benign symptoms, a higher proportion of grade 1 tumors, and favorable outcomes; however, there is a small subset of PEMs with extension outside the cranium and spine that require specific considerations for management. Full article
(This article belongs to the Special Issue Combination Therapies for Brain Tumors)
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<p>PRISMA 2020 flow diagram.</p>
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15 pages, 2215 KiB  
Case Report
Primary Prostatic Stromal Sarcoma: A Case Report and Review of the Literature
by Enes Erul, Ömer Gülpınar, Diğdem Kuru Öz, Havva Berber, Saba Kiremitci and Yüksel Ürün
Medicina 2024, 60(12), 1918; https://doi.org/10.3390/medicina60121918 - 22 Nov 2024
Viewed by 307
Abstract
Background and Objectives: Primary prostatic stromal sarcoma is an exceptionally rare urological malignancy, constituting less than 0.1% of all prostatic cancers. It poses a significant clinical challenge due to its aggressive behavior and poor prognosis. Materials and Methods: We report the [...] Read more.
Background and Objectives: Primary prostatic stromal sarcoma is an exceptionally rare urological malignancy, constituting less than 0.1% of all prostatic cancers. It poses a significant clinical challenge due to its aggressive behavior and poor prognosis. Materials and Methods: We report the case of a 34-year-old male who presented with nonspecific lower urinary tract symptoms, including dysuria and increased urinary frequency. The initial diagnostic workup, including digital rectal examination and Magnetic Resonance Imaging (MRI), revealed a lobulated lesion within the prostate. A transurethral resection (TUR) was performed for diagnostic purposes, and histopathological examination revealed a “malignant mesenchymal tumor”. The patient underwent a laparoscopic radical prostatectomy. The pathology report confirmed the diagnosis of prostatic stromal sarcoma. The postoperative follow-up, including systemic CT and MRI, showed no evidence of recurrence or metastasis thus far. Results: Multidisciplinary management is essential for optimizing treatment outcomes in all urologic malignancies; however, it becomes particularly challenging and crucial in rare cases such as primary prostatic stromal sarcoma. In our case, the patient benefited from a coordinated approach involving urology, pathology, and oncology, underscoring the importance of collaborative care for rare and aggressive tumors like this. This case highlights the importance of early detection, complete surgical excision, and consideration of adjuvant therapies, given the aggressive nature of the disease. The role of novel therapeutic strategies, including immunotherapy and targeted therapies, is also discussed in the context of metastatic sarcomas. Conclusions: This case underscores the critical need for a comprehensive, multidisciplinary approach to managing primary prostatic stromal sarcoma. Ongoing research on innovative therapies offers hope for improved outcomes in metastatic stages. Full article
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Figure 1
<p>(<b>a</b>–<b>c</b>). In the T2-weighted image (<b>a</b>), a heterogeneous, well-defined, lobulated nodular lesion is observed, confined to the prostate gland, exhibiting marked hyperintense signal characteristics originating from the midline urethral area and largely filling the left lobe of the prostate gland. In the diffusion-weighted image (<b>b</b>) acquired with a b-value of 2000, focal areas of diffusion restriction are observed within the lesion. The lesion demonstrates intense and heterogeneous enhancement in the early arterial phase (<b>c</b>).</p>
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<p>Histopathological findings of prostatic stromal sarcoma. (<b>A</b>) Invasion of the atypical spindle tumor cells between the metaplastic benign epithelial and glandular structures in a diffuse stromal growth pattern with phyllodes-like and hypercellular areas, ×40, Hematoxylin–Eosin. (<b>B</b>) Hypocellular myxoid areas with round and starry tumor cells, ×100. (<b>C</b>) Increased mitotic activity in high magnification, ×400. (<b>D</b>) Remarkable atypical tripolar mitosis, ×690.</p>
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<p>Immunohistochemical findings of prostatic stromal sarcoma. Diffuse and strong positivity with Vimentin (×150); focal positivity with CD34 (vascular structures as internal control) (×110); infrequent positivity with PR (×220); diffuse positivity with p53 (×150); high proliferation index with Ki67 (×150).</p>
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14 pages, 1732 KiB  
Review
Abscopal Effect with Liver-Directed Therapy: A Review of the Current Literature and Future Directions
by Jonah M. Levine, Alyssar Habib, Mikhail Silk, Greg D. Sacks, Rafael Winograd, Colin S. Hill, Ammar A. Javed, Christopher L. Wolfgang and D. Brock Hewitt
Livers 2024, 4(4), 601-614; https://doi.org/10.3390/livers4040042 - 22 Nov 2024
Viewed by 310
Abstract
The liver is a common site for metastatic disease. In select patients with isolated liver metastases, surgical resection improves survival and may be potentially curative in patients with favorable “tumor biology”. However, when surgical resection is not feasible, liver-directed therapies (LDTs) can also [...] Read more.
The liver is a common site for metastatic disease. In select patients with isolated liver metastases, surgical resection improves survival and may be potentially curative in patients with favorable “tumor biology”. However, when surgical resection is not feasible, liver-directed therapies (LDTs) can also improve outcomes, including survival, in the appropriate clinical situations. LDTs, including hepatic artery infusion, radioembolization, radiation, and ablation techniques, such as thermal ablation and histotripsy, offer local control and potential systemic effects, including the abscopal effect. The abscopal effect occurs when nontargeted, nontreated tumors regress following localized therapy to other tumors. Preclinical and clinical studies suggest that antigen-induced upregulation of key immune regulators plays a central role in this process. Unfortunately, clinical reports of the abscopal effect following LDT are exceedingly rare. However, histotripsy, a noninvasive, nonionizing, and nonthermal ablation technique, may induce an abscopal effect more frequently and robustly than other LDTs. Histotripsy enhances tumor immunogenicity through precise acoustic cavitation that better preserves the local tissue architecture while increasing antigen release, resulting in a robust local and systemic immune response. Ongoing trials are investigating these immunogenic mechanisms and the ability to generate an abscopal effect more reliably with adjuncts such as checkpoint inhibitors. This work has significant implications regarding the management of patients with liver metastasis. Full article
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<p>Schematic illustration of histotripsy: (<b>a</b>) technical setup of histotripsy; (<b>b</b>) real-time evaluation of treatment; pink dashed circle shows larger region of treatment, white dashed circle shows center of treatment where the hyperechoic region is due to the presence of bubbles (<b>c</b>) post-treatment visualization; white dashed circle shows hypoechoic region due to liquification (<b>d</b>) liquified region of the organ; (<b>e</b>) histology [<a href="#B12-livers-04-00042" class="html-bibr">12</a>].</p>
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<p>Treatment of targeted tumor and mechanism of distant control. The figure on the left shows how a targeted tumor (pink) can cause a systemic effect leading to a reduction in distant tumors (red) [<a href="#B63-livers-04-00042" class="html-bibr">63</a>].</p>
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<p>Proposed mechanisms for the immune activation of histotripsy [<a href="#B63-livers-04-00042" class="html-bibr">63</a>].</p>
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8 pages, 3331 KiB  
Article
Computational Simulation of LAVA Treatment of Thyroid Eye Disease Predicts Soft Tissue Outcome Comparable to Two-Wall Resection
by Matthias Krause and Evgeny Gladilin
Bioengineering 2024, 11(12), 1181; https://doi.org/10.3390/bioengineering11121181 - 22 Nov 2024
Viewed by 315
Abstract
Thyroid eye disease (TED) is a common extrathyroidal manifestation of hyperthyroidism, typically associated with Graves’ disease (GD). This condition can cause severe functional limitations as well as significant aesthetic concerns. Treatment for TED patients aims to restore functionality and address aesthetic concerns. Surgical [...] Read more.
Thyroid eye disease (TED) is a common extrathyroidal manifestation of hyperthyroidism, typically associated with Graves’ disease (GD). This condition can cause severe functional limitations as well as significant aesthetic concerns. Treatment for TED patients aims to restore functionality and address aesthetic concerns. Surgical TED treatment is usually performed by orbital wall resection, which effectively decompresses intraorbital tissues and corrects the orbital/ocular disorders. Several different scenarios of surgical TED treatment including one-, two-, and three-wall resections are known. More recently, a new minimally invasive technique, the so-called lateral valgization (LAVA) of the orbital wall, was reported to show promising results comparable to conventional wall resection techniques. Due to the relatively limited data on TED treatment, only a few quantitative investigations of alternative TED surgery scenarios exist. In this feasibility study, we estimate the soft tissue outcome of LAVA treatment using computational simulation. Our experimental results show that the amount of intraorbital tissue released into the extraorbital space by LAVA treatment is comparable with the outcome of two-wall resection. Our computational simulation confirms previously reported isolated clinical findings suggesting that the minimally invasive LAVA approach represents an attractive alternative to conventional wall resection approaches for surgical TED treatment. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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<p>Example of TED treatment using the two-wall resection approach. A central CT slice of a TED patient after two-wall resection treatment (lateral and medial) at both sites. The close relationship of the temporalis muscle to the rectus lateralis muscle can be seen; thus, the laterally open orbit (red arrow) can be closed by the function of the temporalis muscle.</p>
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<p>Example of LAVA treatment. A central CT slice of a TED patient who underwent a LAVA treatment. Valgization of the lateral wall at both sites prevents herniation of the temporalis muscle (red arrows) and keeps the new lateral orbital space open.</p>
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<p>Overview of 3D modeling and simulation of LAVA treatment. (<b>a</b>) Side view at the patient skull (transparent) and orbital models (blue–red) including the patch on the right lateral wall (green) to be relocated in the course of the LAVA treatment; (<b>b</b>) two-tissue material model of the orbital tissues (red—muscles, blue—fat) with the patch of the lateral wall to be relocated (green); (<b>c</b>) front view at the LAVA treatment plan with valgization of the bone fragment of the right lateral wall (green); (<b>d</b>) top-view visualization of valgization of the lateral wall followed by an outflow of orbital tissue (indicated by the displacement vectors).</p>
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24 pages, 400 KiB  
Review
Current Management of Locally Recurrent Rectal Cancer
by Claudio Coco, Gianluca Rizzo, Luca Emanuele Amodio, Donato Paolo Pafundi, Federica Marzi and Vincenzo Tondolo
Cancers 2024, 16(23), 3906; https://doi.org/10.3390/cancers16233906 (registering DOI) - 21 Nov 2024
Viewed by 254
Abstract
Locally recurrent rectal cancer (LRRC), which occurs in 6–12% of patients previously treated with surgery, with or without pre-operative chemoradiation therapy, represents a complex and heterogeneous disease profoundly affecting the patient’s quality of life (QoL) and long-term survival. Its management usually requires a [...] Read more.
Locally recurrent rectal cancer (LRRC), which occurs in 6–12% of patients previously treated with surgery, with or without pre-operative chemoradiation therapy, represents a complex and heterogeneous disease profoundly affecting the patient’s quality of life (QoL) and long-term survival. Its management usually requires a multidisciplinary approach, to evaluate the several aspects of a LRRC, such as resectability or the best approach to reduce symptoms. Surgical treatment is more complex and usually needs high-volume centers to obtain a higher rate of radical (R0) resections and to reduce the rate of postoperative complications. Multiple factors related to the patient, to the primary tumor, and to the surgery for the primary tumor contribute to the development of local recurrence. Accurate pre-treatment staging of the recurrence is essential, and several classification systems are currently used for this purpose. Achieving an R0 resection through radical surgery remains the most critical factor for a favorable oncologic outcome, although both chemotherapy and radiotherapy play a significant role in facilitating this goal. If a R0 resection of a LRRC is not feasible, palliative treatment is mandatory to reduce the LRRC-related symptoms, especially pain, minimizing the effect of the recurrence on the QoL of the patients. The aim of this manuscript is to provide a comprehensive narrative review of the literature regarding the management of LRRC. Full article
(This article belongs to the Special Issue Advances in Cancer Therapeutics)
14 pages, 991 KiB  
Article
Upfront Surgery vs. Endoscopic Stenting Bridge to Minimally Invasive Surgery for Treatment of Obstructive Left Colon Cancer: Analysis of Surgical and Oncological Outcomes
by Mauro Marzano, Paolo Prosperi, Gian Luca Grazi, Fabio Cianchi, Luca Talamucci, Damiano Bisogni, Lapo Bencini, Manuela Mastronardi, Tommaso Guagni, Agostino Falcone, Jacopo Martellucci, Carlo Bergamini and Alessio Giordano
Cancers 2024, 16(23), 3895; https://doi.org/10.3390/cancers16233895 - 21 Nov 2024
Viewed by 294
Abstract
Background: Left colon cancer obstruction treatment is a debated topic in the literature. Stent placement is effective as a bridge-to-surgery strategy, but there are some concerns about the oncological safety for the reported higher risk of local and peritoneal recurrence. This study aims [...] Read more.
Background: Left colon cancer obstruction treatment is a debated topic in the literature. Stent placement is effective as a bridge-to-surgery strategy, but there are some concerns about the oncological safety for the reported higher risk of local and peritoneal recurrence. This study aims to compare the surgical and oncological outcomes of patients treated with stent followed by elective surgery with those treated with primary resection. Methods: This is a retrospective observational study. We included patients of both sexes, ≥18 years old, with a histological diagnosis of intestinal adenocarcinoma, and admitted to our hospital for left colon cancer obstruction demonstrated by CT scan without metastasis or perforation. They were treated through primary resection (PR) or stent placement followed by elective surgery (SR). The two groups were compared for general characteristics, surgical outcomes, and oncological outcomes (metastasis and local recurrence) at 30 days, 90 days, 1 year, and 3 years. Post-operative quality of life (QoL) was also investigated. Results: The SR group showed a shorter hospital stay, a lower post-operative mortality, a lower stoma rate at 1 year, and a higher number of minimally invasive procedures. Oncological outcomes were not different compared to the PR group. The SR group demonstrated better QoL in two out of six items on the EQ-5D-5L test. Conclusions: Stent placement as a bridge-to-surgery strategy is feasible and provides better surgical outcomes in terms of post-operative complications, surgical approach, stoma rate, and QoL. Oncological outcomes were not reported differently, but further studies should be conducted to better evaluate this aspect. Full article
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<p>EQ-5D-5L test.</p>
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<p>The 1-year Kaplan–Meier survival estimates.</p>
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<p>The 3-year Kaplan–Meier survival estimates.</p>
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11 pages, 6253 KiB  
Case Report
The Microsurgical Resection of an Arteriovenous Malformation in a Patient with Thrombophilia: A Case Report and Literature Review
by Corneliu Toader, Felix-Mircea Brehar, Mugurel Petrinel Radoi, Matei Serban, Razvan-Adrian Covache-Busuioc, Luca-Andrei Glavan, Alexandru Vlad Ciurea and Nicolaie Dobrin
Diagnostics 2024, 14(23), 2613; https://doi.org/10.3390/diagnostics14232613 - 21 Nov 2024
Viewed by 221
Abstract
Background/Objectives: Arteriovenous malformations (AVMs) are complex vascular anomalies that can present with significant complications, including intracranial hemorrhage. This report presents the case of a 36-year-old female with Prothrombin G20210A mutation-associated thrombophilia, highlighting its potential impact on AVM pathophysiology and management. Methods: The patient [...] Read more.
Background/Objectives: Arteriovenous malformations (AVMs) are complex vascular anomalies that can present with significant complications, including intracranial hemorrhage. This report presents the case of a 36-year-old female with Prothrombin G20210A mutation-associated thrombophilia, highlighting its potential impact on AVM pathophysiology and management. Methods: The patient presented with a right paramedian intraparenchymal frontal hematoma, left hemiparesis, and seizures. Cerebral angiography identified a ruptured right parasagittal frontal AVM classified as Spetzler–Martin Grade II. A right interhemispheric frontal craniotomy was performed, enabling microsurgical resection of the AVM. Intraoperative findings included evacuation of a subcortical hematoma and excision of a 20 mm AVM nidus with arterial feeders from the A4 segment of the anterior cerebral artery and a single venous drainage into the superior sagittal sinus. Results: Postoperative recovery was favorable, with significant neurological improvement. The patient demonstrated resolution of hemiparesis and a marked reduction in seizure activity. The hypercoagulable state associated with Prothrombin G20210A mutation was identified as a contributing factor in the thrombosis of the AVM’s draining vein, potentially leading to increased venous pressure, rupture, and hemorrhage. Conclusions: This case underscores the importance of recognizing thrombophilia in patients with AVMs for optimal surgical planning and complication management. Despite the challenges posed by the hypercoagulable condition, microsurgical resection proved to be a viable and effective treatment option. Further research is warranted to elucidate the relationship between thrombophilic disorders and AVMs to enhance patient management strategies and outcomes. Full article
(This article belongs to the Special Issue Vascular Malformations: Diagnosis and Management)
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<p>Preoperative 2D digital subtraction angiography. 2D DSA showcases the parasagittal frontal AVM, marked by the white arrows. The AVM, indicated by white arrows in both images, is lo-cated in the parasagittal region. The left image highlights the arterial phase, where the feeding arteries are visible as they supply the AVM. The right image captures the venous phase, demon-strating the early venous drainage of the AVM. The dense vascular network and abnormal con-nections between the arteries and veins, typical of an AVM, are clearly seen. These images provide critical details for assessing the AVM’s structure, including the arterial feeders and venous out-flow, which are essential for planning surgical or interventional treatment.</p>
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<p>Preoperative 2D digital subtraction angiography in both the profile and frontal view which depicts the AVM, marked by the white arrows.</p>
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<p>Preoperative 3D DSA rotational angiography, with the reconstruction of rotational DSA depicting the 3D topography of the arteriovenous malformation with an arterial A4 feeder from the anterior cerebral artery and single venous drainage into the superior sagittal sinus.</p>
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<p>CT scan conducted just before patient discharge shows no signs of hemorrhage.</p>
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<p>Eight-month follow-up CT scan indicates no hemorrhage.</p>
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3 pages, 1051 KiB  
Interesting Images
“Rosary Sign” at Somatostatin Receptor PET in a Case of Recurrent Meningioma
by Cesare Michele Iacovitti, Davide Giovanni Bosetti, Barbara Muoio, Marco Cuzzocrea, Gaetano Paone and Giorgio Treglia
Diagnostics 2024, 14(22), 2608; https://doi.org/10.3390/diagnostics14222608 - 20 Nov 2024
Viewed by 322
Abstract
We present the case of a 60-year-old male with recurrent atypical meningioma in the right parietal lobe, previously treated with surgery and radiation therapy. Magnetic resonance imaging (MRI) performed 5 years after radiation therapy suggested a possible recurrence. A somatostatin receptor positron emission [...] Read more.
We present the case of a 60-year-old male with recurrent atypical meningioma in the right parietal lobe, previously treated with surgery and radiation therapy. Magnetic resonance imaging (MRI) performed 5 years after radiation therapy suggested a possible recurrence. A somatostatin receptor positron emission tomography/computed tomography (SR-PET/CT) scan with Gallium-68 DOTATATE was performed to confirm this suspicion. SR-PET/CT confirmed the presence of recurrent meningioma, showing a novel “rosary sign” with multiple adjacent areas of focal tracer uptake along the resection margins of the previous surgical site in the right parietal region. This novel imaging pattern improved diagnostic accuracy by detailing disease extent and identifying additional lesions not visible via MRI. Given the failure of prior treatments and high SR expression, peptide receptor radionuclide therapy (PRRT) was proposed as a therapeutic option for the patient. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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<p>A 60-year-old male with recurrent atypical meningioma, previously treated with surgery (6 years before) and radiation therapy for a local recurrence (5 years before), underwent segmental brain somatostatin receptor positron emission tomography/computed tomography (SR-PET/CT) for restaging after magnetic resonance imaging (MRI) findings suggested a possible recurrence. SR-PET/CT was performed 60 min after the injection of 200 MBq of Gallium-68 DOTATATE (a radiolabeled somatostatin analogue), and PET images were also fused with the recent MRI images. SR-PET image analysis was performed by using qualitative criteria: areas of increased radiopharmaceutical uptake compared to the background, excluding the sites of physiological radiotracer uptake, were considered abnormal. Furthermore, semi-quantitative PET image analysis was performed by using the maximal standardized uptake value (SUV<sub>max</sub>). Axial and coronal T1-weighted MRI images (<b>A1</b>,<b>B1</b>), fused PET/MRI images (<b>A2</b>,<b>B2</b>), fused PET/CT images (<b>A3</b>,<b>B3</b>) and maximum intensity projection PET images (lateral view (<b>C1</b>), anterior view (<b>C2</b>)) revealed a novel “rosary sign” with multiple adjacent areas of focal abnormal radiopharmaceutical uptake (red arrows) along the resection margins of the previous surgical site in the right parietal region, corresponding to hyperintense lesions at T1-weighted MRI (green arrows), while the pituitary showed physiological tracer uptake (blue arrows). The “rosary sign” was particularly relevant because it highlighted multiple foci of abnormal radiopharmaceutical uptake linked together, suggesting disease recurrence and confirming the suspicion raised by MRI, as well as identifying a higher number of lesions. The highest SUV<sub>max</sub> of the meningiomatous lesions was 16.9. Due to the high SR expression demonstrated by SR-PET/CT with this novel imaging pattern and considering progressing/recurrent disease after multiple treatments, this patient was addressed with peptide receptor radionuclide therapy (PRRT) [<a href="#B1-diagnostics-14-02608" class="html-bibr">1</a>,<a href="#B2-diagnostics-14-02608" class="html-bibr">2</a>,<a href="#B3-diagnostics-14-02608" class="html-bibr">3</a>]. SR-PET/CT is indicated for the differential diagnosis of brain lesions suspicious for meningiomas, delineation of meningioma extent, detection multifocal disease/extracranial metastases, and monitoring of disease progression or diagnosis of recurrence, playing a crucial role in these clinical assessments [<a href="#B1-diagnostics-14-02608" class="html-bibr">1</a>,<a href="#B2-diagnostics-14-02608" class="html-bibr">2</a>,<a href="#B4-diagnostics-14-02608" class="html-bibr">4</a>,<a href="#B5-diagnostics-14-02608" class="html-bibr">5</a>,<a href="#B6-diagnostics-14-02608" class="html-bibr">6</a>,<a href="#B7-diagnostics-14-02608" class="html-bibr">7</a>,<a href="#B8-diagnostics-14-02608" class="html-bibr">8</a>,<a href="#B9-diagnostics-14-02608" class="html-bibr">9</a>]. PRRT is a well-tolerated treatment option for both meningiomas and neuroendocrine tumors with high somatostatin receptor expression. Patients with progressive/recurrent/treatment refractory meningiomas and increased SR expression are ideal candidates for PRRT if a previous SR-PET/CT demonstrates high SR expression [<a href="#B1-diagnostics-14-02608" class="html-bibr">1</a>,<a href="#B2-diagnostics-14-02608" class="html-bibr">2</a>,<a href="#B3-diagnostics-14-02608" class="html-bibr">3</a>].</p>
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11 pages, 500 KiB  
Systematic Review
Electrochemotherapy in the Locoregional Treatment of Metastatic Colorectal Liver Metastases: A Systematic Review
by Pierluigi Barbieri, Alessandro Posa, Valentina Lancellotta, David C. Madoff, Alessandro Maresca, Patrizia Cornacchione, Luca Tagliaferri and Roberto Iezzi
Curr. Oncol. 2024, 31(11), 7403-7413; https://doi.org/10.3390/curroncol31110546 - 20 Nov 2024
Viewed by 273
Abstract
Background: The global incidence of secondary liver cancer is rising due to multiple risk factors, presenting significant challenges in public health. Similarly, colorectal cancer (CRC) remains a leading cause of cancer-related mortality with the development of frequent liver metastases. Surgical resection of CRC [...] Read more.
Background: The global incidence of secondary liver cancer is rising due to multiple risk factors, presenting significant challenges in public health. Similarly, colorectal cancer (CRC) remains a leading cause of cancer-related mortality with the development of frequent liver metastases. Surgical resection of CRC liver metastases is only suitable for a limited subset of patients, necessitating alternative nonsurgical treatments such as electrochemotherapy (ECT); Methods: This review adhered to the S.P.I.D.E.R. framework. Systematic searches of PubMed, Cochrane, and Scopus databases were conducted for studies published between 2003 and 2023, following PRISMA guidelines. Inclusion criteria were full-text clinical studies in English focusing on ECT-treated CRC liver metastases, excluding reviews, editorials, and non-clinical papers. The GRADE approach was utilized to assess evidence quality, considering study limitations, consistency, and other factors; Results: From 38 identified articles, 4 met the inclusion criteria, encompassing 78 patients and 128 treated lesions. The studies demonstrated variability in design and follow-up duration (3–11 months). Complete response (CR) rates ranged from 33.3% to 63.0%, while progression disease (PD) rates were high, ranging from 23.0% to 55.6%. Median overall survival (OS) spanned 11.3 to 29.0 months. No severe ECT-related complications were reported. Conclusions: ECT appears to be a safe and effective modality for the treatment of CRC liver metastases, especially for lesions unsuitable for other ablative techniques. Further prospective and randomized studies are essential to better define the role of ECT in managing CRC liver metastases and to compare its efficacy with other ablative methods. Full article
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<p>PRISMA flowchart.</p>
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17 pages, 1523 KiB  
Article
Prognostic Role of Invasion-Related Extracellular Matrix Molecules in Diffusely Infiltrating Grade 2 and 3 Astrocytomas
by László Szivos, József Virga, Zoltán Mészár, Melinda Rostás, Andrea Bakó, Gábor Zahuczki, Tibor Hortobágyi and Álmos Klekner
Brain Sci. 2024, 14(11), 1157; https://doi.org/10.3390/brainsci14111157 - 20 Nov 2024
Viewed by 349
Abstract
Background: Astrocytoma, an IDH-mutant is a common primary brain tumor. Total surgical resection is not feasible due to peritumoral infiltration mediated by extracellular matrix (ECM) molecules. Methods: This study aimed at determining the expression pattern of ECM molecules in different prognostic groups of [...] Read more.
Background: Astrocytoma, an IDH-mutant is a common primary brain tumor. Total surgical resection is not feasible due to peritumoral infiltration mediated by extracellular matrix (ECM) molecules. Methods: This study aimed at determining the expression pattern of ECM molecules in different prognostic groups of WHO grade 2 and grade 3 patients and identifying the effect of onco-radiotherapy on tumor cell invasion of grade 3 patients. Gene and protein expression of ECM molecules was determined by qRT-PCR and immunohistochemistry, respectively. Results: In the different prognostic groups of grade 2 tumors HMMR, IDH-1, MKI-67, PDGF-A and versican, in grade 3 tumors integrin α-3, and in both groups integrin α-3 and IDH-1 mRNA expression was significantly different. Regarding protein expression, only integrin αV expression changed significantly in the prognostic groups of grade 2 tumors. Conclusions: Based on the invasion spectrum determined by this joint gene and protein expression analysis, there was a sensitivity of 87.5% and a negative predictive value of 88.9% regarding the different prognostic groups of grade 2 astrocytoma. For grade 3 tumors, the applied standard oncotherapeutic modalities apparently lacked significant anti-invasive effects. Full article
(This article belongs to the Special Issue Brain Tumors: From Molecular Basis to Therapy)
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<p>Kaplan–Meier curve in terms of progression-free survival-1 time of different prognostic groups in Grade-2 astrocytomas. Group A: patients with poor prognosis; Group B: patients with better prognoses.</p>
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<p>Invasion spectrum of invasion-related extracellular matrix molecules in case of Grade-2 diffuse astrocytomas. Relative expression: Quotient of average mRNA expression of each ECM molecule’s natural logarithm (ln <span class="html-italic">x</span>).</p>
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<p>Immunohistochemical staining of integrin α-3 and IDH-1 (<b>left</b>) and brevican and MDM2 (<b>right</b>) in Gr 3 astrocytaer tumors. The patient in grade 3 group A [No. 1521-<a href="#app1-brainsci-14-01157" class="html-app">Supplementary Materials Table S2A</a>] did not receive any previous treatment, while the patient in grade 3 group B [No. 501-<a href="#app1-brainsci-14-01157" class="html-app">Supplementary Materials Table S2B</a>] received whole brain radiation therapy (WBRT).</p>
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